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NGF and GDNF ameliorate the increase in ATF3 expression which occurs in dorsal root ganglion cells in response to peripheral nerve injury.
Eur J Neurosci. 2004 Mar; 19(6):1437-45.EJ

Abstract

Activating transcription factor-3 (ATF3) is a member of the ATF/CREB transcription factor superfamily and is induced in dorsal root ganglion (DRG) cells after nerve injury. In order to study the regulation of ATF3, we have examined the effect of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) on ATF3 expression. In untreated rats, sciatic nerve transection induced ATF3 immunoreactivity in 82% of L4 DRG cells at 14 days after axotomy. Intrathecal delivery of NGF or GDNF for 2 weeks commencing immediately after injury reduced the ATF3 expression to 35 and 23% of DRG cells, respectively. Cell size analysis indicated that NGF had protected a population of mainly small- to medium-sized cells, but that the GDNF had protected a population of both small and large cells. This effect was confirmed by double labelling for P2X(3), CGRP and 200 kDa neurofilament, markers for small peptide-poor cells, peptide-rich cells and large cells, respectively. Thus GDNF reduced the percentage of ATF3-immunoreactive P2X(3) cells from 70 to 4%, and the percentage of ATF3-immunoreactive neurofilament cells from 63 to 24%. NGF was less effective than GDNF in reducing ATF3 expression in these cell types, but reduced the percentage of ATF3-immunoreactive CGRP cells from 10% to < 1%. These results show that ATF3 expression in specific populations of DRG cells can be modulated by exogenous supplementation of specific trophic factors, and suggest that ATF3 expression may normally be induced by the loss of target-derived NGF and GDNF.

Authors+Show Affiliations

Neuroscience Centre, Bart's & The London School of Medicine & Dentistry, Queen Mary University of London, Mile End Road, London E1 4NS, UK. s.a.averrill@qmul.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15066140

Citation

Averill, Sharon, et al. "NGF and GDNF Ameliorate the Increase in ATF3 Expression Which Occurs in Dorsal Root Ganglion Cells in Response to Peripheral Nerve Injury." The European Journal of Neuroscience, vol. 19, no. 6, 2004, pp. 1437-45.
Averill S, Michael GJ, Shortland PJ, et al. NGF and GDNF ameliorate the increase in ATF3 expression which occurs in dorsal root ganglion cells in response to peripheral nerve injury. Eur J Neurosci. 2004;19(6):1437-45.
Averill, S., Michael, G. J., Shortland, P. J., Leavesley, R. C., King, V. R., Bradbury, E. J., McMahon, S. B., & Priestley, J. V. (2004). NGF and GDNF ameliorate the increase in ATF3 expression which occurs in dorsal root ganglion cells in response to peripheral nerve injury. The European Journal of Neuroscience, 19(6), 1437-45.
Averill S, et al. NGF and GDNF Ameliorate the Increase in ATF3 Expression Which Occurs in Dorsal Root Ganglion Cells in Response to Peripheral Nerve Injury. Eur J Neurosci. 2004;19(6):1437-45. PubMed PMID: 15066140.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NGF and GDNF ameliorate the increase in ATF3 expression which occurs in dorsal root ganglion cells in response to peripheral nerve injury. AU - Averill,Sharon, AU - Michael,Gregory J, AU - Shortland,Peter J, AU - Leavesley,Rachel C, AU - King,Von R, AU - Bradbury,Elizabeth J, AU - McMahon,Stephen B, AU - Priestley,John V, PY - 2004/4/7/pubmed PY - 2004/5/29/medline PY - 2004/4/7/entrez SP - 1437 EP - 45 JF - The European journal of neuroscience JO - Eur. J. Neurosci. VL - 19 IS - 6 N2 - Activating transcription factor-3 (ATF3) is a member of the ATF/CREB transcription factor superfamily and is induced in dorsal root ganglion (DRG) cells after nerve injury. In order to study the regulation of ATF3, we have examined the effect of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) on ATF3 expression. In untreated rats, sciatic nerve transection induced ATF3 immunoreactivity in 82% of L4 DRG cells at 14 days after axotomy. Intrathecal delivery of NGF or GDNF for 2 weeks commencing immediately after injury reduced the ATF3 expression to 35 and 23% of DRG cells, respectively. Cell size analysis indicated that NGF had protected a population of mainly small- to medium-sized cells, but that the GDNF had protected a population of both small and large cells. This effect was confirmed by double labelling for P2X(3), CGRP and 200 kDa neurofilament, markers for small peptide-poor cells, peptide-rich cells and large cells, respectively. Thus GDNF reduced the percentage of ATF3-immunoreactive P2X(3) cells from 70 to 4%, and the percentage of ATF3-immunoreactive neurofilament cells from 63 to 24%. NGF was less effective than GDNF in reducing ATF3 expression in these cell types, but reduced the percentage of ATF3-immunoreactive CGRP cells from 10% to < 1%. These results show that ATF3 expression in specific populations of DRG cells can be modulated by exogenous supplementation of specific trophic factors, and suggest that ATF3 expression may normally be induced by the loss of target-derived NGF and GDNF. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/15066140/NGF_and_GDNF_ameliorate_the_increase_in_ATF3_expression_which_occurs_in_dorsal_root_ganglion_cells_in_response_to_peripheral_nerve_injury_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0953-816X&amp;date=2004&amp;volume=19&amp;issue=6&amp;spage=1437 DB - PRIME DP - Unbound Medicine ER -